The targeting and removal or destruction of malignant cells in a body is an ongoing battle in the war against cancer. As an option to the surgical removal of malignant cells, modern medical advances have developed treatments, such as chemical and radiation treatments, that are designed to induce in situ programmed cell death in malignant cells. Programmed cell death refers generally to the self-destruction of cells (cell suicide), for example, by apoptosis, autophagy, and necroptosis. References herein to apoptosis will be understood to apply to other forms of programmed cell death. The challenge in existing procedures to induce apoptosis is to achieve acceptable levels of malignant cell death, without undue collateral damage to healthy cells.
Apoptosis is distinguished from necrosis. Necrosis occurs, for example, when a cell is sufficiently damaged by an external factor, such as poison, a bodily injury, or an infection. When cells die from necrosis, it may cause inflammation that can cause further damage to the body. Apoptosis, on the other hand, is relatively less stressful to the body, following a controlled, predictable routine. When the cell is induced to undergo programmed cell death proteins called caspases (cysteine-aspartic proteases, cysteine aspartases, or cysteine-dependent aspartate-directed proteases) break down the cellular components needed for survival, and spur production of deoxyribonuclease enzymes known as DNases, which destroy the DNA in the nucleus of the cell. Apoptosis is a natural and ongoing process essential to human development.
Cells that go through apoptosis die or self-destruct in response to signals within the body. For example, when cells recognize viruses and gene mutations, they may initiate programmed cell death to prevent the damage from spreading. When cells are under stress, apoptosis can occur. Anti-cancer drugs and radiation, for example, typically work by triggering apoptosis in diseased cells.
If a cell sustains irreparable internal damage the cell will initiate apoptosis. In particular, a damaging mechanical disruption to a cell can induce the cell to initiate apoptosis. It would be beneficial if malignant cells in a body could be targeted and selectively mechanically agitated to induce damage sufficient to cause the target cell to initiate programmed cell death without rendering the cells necrotic. Nano-actuators and methods are disclosed herein to initiate such apoptosis to remove cancer cells. In particular, the disclosed methods provide a treatment that does not require irradiation or poisoning of the body (or reduces the amount of irradiation or poisoning) thereby avoiding or mitigating unwanted collateral health effects that may be caused by such treatments.
The Taya group at the University of Washington has developed a number of macro-scale ferromagnetic shape memory alloy (FSMA) actuator. One of the FSMA actuators is formed from an iron-palladium alloy (FePd) as a helical spring. The FePd spring can be actuated or compressed using an externally applied magnetic gradient field. The mechanism of the actuation of the FePd spring is believed to be a chain-reaction sequence wherein (i) the applied magnetic gradient field induces (ii) a magnetic force, which (iii) results in a stress-induced diffusionless martensite phase transformation in the FePd, and (iv) as a result of the phase change, the Young's modulus of the spring is reduced, enabling a large deformation in the spring. The above sequential chain-reaction takes place within a very short time.
Actuators are relatively simple mechanical components that are often incorporated into more complex mechanical systems. Shape memory alloys are alloys that may transition or transform between two different phases. Large (macro-scale) linear actuators having a helical spring formed at least partially from an FSMA are known in the art. For example, one of the present inventors has disclosed an FSMA spring actuator in U.S. Pat. No. 7,104,056, to Taya et al., which is hereby incorporate by reference in its entirety. The disclosed spring actuator includes an FSMA coil, a hybrid magnetic trigger including both a permanent magnet and an electromagnet, and a yoke configured to couple magnetic flux from the magnet to the spring.